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Quick guide
Jellyfish nervous
systems
Takeo Katsuki
and Ralph J. Greenspan
What are jellyfish? The term jellyfish
generally refers to the umbrellashaped gelatinous zooplanktons that
belong to Scyphozoa (true jellyfish),
Staurozoa (stalked jellyfish), Cubozoa
(box jellyfish), and Hydrozoa of Phylum
Cnidaria. Their sizes, shapes, and
habitats are diverse. Sexually mature
jellyfish range from millimeters to
meters in diameter, and they can be
found almost anywhere in the ocean
from the arctic to the tropics and
from the deep sea to the shoreline
(some even live in freshwater).
Despite the substantial variety of their
morphologies, some features are
shared in common. First, they possess
cnidocytes or stinging cells with
which they capture prey and protect
themselves from predators. Second,
they have only one external opening
for food intake, waste disposal, and
gamete discharge. Third, they are
radially symmetric around the single
oral/aboral body axis, typically with a
symmetry order of four or more.
What is their life cycle? The life
cycle of jellyfish consists of two
main stages: polyp and medusa.
The polyp is a sessile form usually
stalk-like or funnel-like in shape.
Polyps attach themselves to a solid
surface and reproduce asexually
by budding, dividing, or podocyst
formation. When conditions, for
example, nutrition, temperature,
salinity and lighting, are favorable,
polyps produce free-swimming
medusae. In most scyphozoans, a
single polyp gives rise to multiple
immature medusae or ephyrae by
horizontal division, a process termed
strobilation. In contrast, polyps
of Hydrozoa and Cubozoa do not
undergo strobilation; rather, a single
medusa metamorphoses or buds out
from the stalk of a polyp. In general,
a medusa has a radially symmetric
bell or umbrella. Contraction of the
subumbrella muscles squeezes the
bell and generates the thrust for
swimming. Mature medusae, usually
gonochoristic (being either male or
female), produce eggs or sperms for
sexual reproduction. Fertilized eggs
develop into planula larvae, which
swim around by means of their cilia
until they settle on a solid surface
to transform into polyps, and the
cycle restarts. The order of the life
cycle, however, is not absolute. Some
species skip the polyp stage or even
revert from medusa to polyp without
undergoing sexual reproduction.
Do they have brains? No, jellyfish
have no single centralized brain.
Instead, they have radially distributed
nervous systems that are adapted
to their unique body plan. Although
their nervous system is relatively
simple, a common misunderstanding
is that all jellyfish have only a diffuse
nerve net in which neurons are found
homogeneously spread apart. In fact,
most jellyfish species show some
degree of neuronal condensation
that serves as an integrative nervous
system. As little is known about the
nervous system of stauromedusae,
here we focus on scyphomedusae,
cubomedusae, and hydromedusae.
What do their nervous systems look
like? Of the three medusozoan clades,
the nervous system of scyphomedusae
exhibits the most diffuse organization.
There are three major neuronal
components that are known to be
physiologically and histologically
distinct in the Scyphozoa nervous
system: rhopalia, the motor nerve net,
and the diffuse nerve net (Figure 1A).
The rhopalium is the sensory
structure that contains ocelli
(pigmented photosensitive structures),
statocysts (gravity receptors), and
pacemaker neurons that set the
basic swim rhythm. The neurons
in a rhopalium form several
morphologically and molecularly
distinct populations, some of which
are interconnected via commissures,
locally exhibiting a bilaterally
symmetrical organization (Figure 1B).
Most scyphozoans have eight or
more rhopalia, the number of which
is typically in multiples of four, around
the bell margin.
The motor nerve net of
scyphomedusae is the network
of neurons that directly activates
muscle contraction in response to
the signals from the pacemakers.
Neurons of the motor nerve net largely
orient randomly and cover the entire
subumbrella muscle sheets, and they
form chemical synapses at the point
of intersection. Because the synapses
among these neurons are bidirectional,
transmission of excitation is nonpolarized; this allows for throughconduction of the entire nerve net,
thus broad, synchronized contraction
of the swimming muscles.
The diffuse nerve net consists
of a neuronal group that generally
has immunoreactivity to antibodies
against neuropeptides that terminate
in arginine-phenylalanine (known as
RFamide peptides). Activities of the
diffuse nerve net induce marginal
tentacle contraction but not muscle
contraction on its own. The diffuse
nerve net is believed to relay sensory
information to the musculature
indirectly by affecting the pacemaker
activities, and directly by providing
modulatory input to the musculature.
Are there any more elaborations? The
neuronal organization of cubomedusae
is similar to that of scyphomedusae
in the sense that they have nerve
nets and rhopalia (hydromedusae
do not have rhopalia); however, its
degree of neuronal condensation and
integration is in another league. As
the name depicts, Cubozoans have
a squarish shape with four tentacles
and four rhopalia. Each rhopalium
contains six eyes of four different
types, two of which (the upper lens
eye and the lower lens eye) are highly
developed image-forming eyes with
cornea, pupil, lens, and retina, much
like our own (Figure 1C). Several
histologically and anatomically
discrete neuronal populations are
found, most of which are situated in
a bilaterally symmetrical manner with
commissures connecting two sides of
the rhopalium. Neighboring rhopalia
are connected via a ring nerve (RN
in Figure 1C), a condensed array
of neuronal tracts that is believed
to integrate the swim system, the
visual system, and the tentacle
system. The ring nerve consists of
three anatomically different types of
neurites that are interconnected by
chemical synapses. In some parts of
the ring nerve, neurons are divided
into compartments by extensions from
epithelial cells, which may provide
electrical insulation between neurites.
Do all jellyfish depend on nerve nets?
No, some hydromedusae lack nerve
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nets. Their neurons are confined to
the inner and outer nerve rings that
run around the bell margin. These
nerve rings consist of multiple parallel
neuronal pathways that process
different sensory inputs such as light,
gravity, and touch. Pacemaker neurons
are also located in the nerve rings. One
Hydrozoa species, Aglantha digitale,
has been shown to have at least 14
physiologically distinct pathways
in the nerve rings (Figure 1D). In
hydromedusae, broad, synchronized
contraction of subumbrella muscles
is achieved by electrical coupling of
muscles through gap junctions (gap
junctions are found only in Hydrozoa).
In Aglantha, however, besides the
electrical coupling among muscles,
motor commands around the ring
nerve are transmitted to the muscle
sheets via neuronal tracts that run up
radially and then laterally along the
subumbrella muscles. Thus, jellyfish
from different clades, or even within
a clade, provide a broad spectrum of
strategies for neuronal integration.
What behavioral repertoires do
they have? Known behaviors of
scyphomedusae include sun compass
navigation, diel vertical migration,
avoidance of low salinity, escape from
contacts with predators, and formation
of aggregates. Although the neuronal
bases for these behaviors are poorly
understood, scyphomedusae appear
to respond to various stimuli such
as gravity, light, salinity, touch, and
chemicals.
Cubomedusae demonstrate a richer
repertoire of vision-based behaviors,
as expected from their state-of-theart light-sensing organs. Tripedalia
cystophora look up through the water
surface with their upper lens eyes, and
direct themselves to the mangrove
canopy, their preferred habitat.
Laboratory studies have shown that
they use visual cues most likely
through their lower lens eyes to locate
light shafts and to avoid obstacles as
they swim. It is presumed that they
do the same thing as they navigate
through the tangled underwater
landscape of mangrove swamps to
find the light shafts where their prey
gather.
These behaviors require not only
accurate vision but also precise
control of speed and direction of
swimming. This is achieved by
modulating pulse frequency, creating
an asymmetry in the opening of the
A
B
te
LC
Rhopalia
O-D
in
A-L
O-C
A-L
O-C
bs
O-P
MNN
DNN
D
C
MG
Rhopalia
P
ULE
RG
RN
LLE
Tentacle
TG
Current Biology
Figure 1. Nervous systems of three medusozoa clades.
(A) Neuromuscular system of Aurelia sp.1 (Scyphozoa) ephyra stained with phalloidin (green) and
antibodies against tyrosinated tubulin (magenta). (B) Schematic diagram of rhopalium nervous
system consisting of terminal (te), intermediate (in), and basal domains (bs). Tyrosinated tubulin
and taurin immunoreactive neurons (green) are connected to motor nerve net. FMRFamide
immunoreactive neurons (blue) are connected to diffuse nerve net. GLWamide immunoreactive
neurons (red) connect the intermediate segment and basal segment. LC, lithocyst (statocyst);
O‑C, oral-central sensory cells; O-D, oral-distal sensory cells; A-L, aboral-lateral group. (Adapted
with permission from Nakanishi et al. (2010).) (C) Tripedalia cystophora showing two rhopalia
and a ring nerve (RN). (Adapted with permission from Skogh et al. (2006).) Inset shows a higher
magnification of a rhopalium with a lower lens eye (LLE), an upper lens eye (ULE), two slit eyes,
and two pit eyes. (Adapted with permission from Nilsson et al. (2005).) (D) Wiring diagram of
Aglantha digitale nervous system. For simplicity, only the swimming system is shown, and
tentacle giant axon (TG, thick pink), motor giant axon (MG, thick red), pacemaker system (P,
green), ring giant axon (RG, blue) are labeled. (Adapted with permission from Mackie (2004).)
bell, and delaying contraction on one
side of the bell in response to light
changes.
One species of Cubozoa, Carybdea
sivickis, has been reported to engage
in courtship rituals, in which a male
grabs a female with its tentacles and
transfers spermatophores onto her
tentacles. Male Carybdea selectively
approach females with conspicuous
velar spots, a putative sign of sexual
maturation, but it is not clear what
sensory modalities are involved in the
recognition.
What is known about neuronal
control of behaviors? One of the most
extensive studies of the neuronal
mechanisms of jellyfish behavior has
been done on the control of swimming
in the hydromedusa Aglantha digitale.
Atypically for hydromedusae, Aglantha
has two different swimming modes:
slow swimming and escape swimming.
Slow swimming is their normal mode,
and is mediated by relatively regular
and weak propulsion of the bell
governed by pacemaker neurons in
the nerve rings. Escape swimming
produces a much stronger contraction
of the bell, and is triggered when one
of the giant neurons in the nerve rings
(ring giant) is excited by mechanical
stimulation of the tentacles. In both
swimming modes, neuronal activity
in the nerve ring is transmitted to the
muscles via the motor giants that run
up the bell.
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The question then is how the same
neurons convey two different sorts of
information. The answer is that motor
giants are capable of generating two
types of action potentials, small/slow
calcium spikes and large/fast sodium
spikes, depending on the degree of
depolarization it receives. As opposed
to the input from the ring giant, the
input from the pacemaker is too low
to trigger the sodium spikes, thus only
inducing slow swimming. In addition to
speed control, Aglantha can steer the
direction of swimming by changing the
shape of the bell opening, the velum.
Many Hydrozoa species, including
Aglantha, can move individual
tentacles to deliver captured prey to
the mouth, which requires coordinated
directional movement of a tentacle,
velum, and manubrium.
What is interesting about jellyfish
nervous systems? Being an outgroup
to Bilateria with complete nervous
systems, jellyfish have been attractive
models for studying the evolution of
nervous systems. For example, by
comparing the expression of genes
involved in the development of sense
organs with that of Bilaterians, one
could ask the evolutionary origin of
sense organs. From a physiological
point of view, the relatively primitive
architecture and behavior of jellyfish
provide an opportunity to address how
sensory inputs and internal information
are integrated to produce coordinated
motor outputs. Intriguingly, despite
the simplicity of their neuronal
organization, jellyfish appear to
have the full battery of molecular
machinery for neurotransmission and
neuromodulation (for example, ion
channels, traditional neurotransmitters,
peptides, amino acids, small
molecules, and their receptors). It
remains largely unknown how this
molecular variety contributes to the
function of jellyfish nervous systems.
Jellyfish have adapted to a wide
range of ecological situations by
developing different sizes, shapes,
and rigidity of the bell and tentacles,
all of which significantly affect the
mechanics of the animals and their
interaction with the fluid environment.
Consequently, the nervous system
must also be matched to the animal’s
physical properties. Comparative
approaches in jellyfish might provide
insights into how neuronal networks
can create a diverse range of
functions from a limited degree of
complexity. It is also of interest that
many medusozoans are capable of
regenerating large portions of their
nervous system, and appear to use
different combinations of stem cells
and committed cell types.
What resources and tools are
available for studying jellyfish
nervous systems? Taking advantage
of the effectively two-dimensional,
transparent, gelatinous body, various
physiological, histological, and
pharmacological approaches have
been employed to examine cellular
and network-level mechanisms in
jellyfish. One of the most important
resources lacking at present is a set
of genetic and molecular tools. For
the Hydromedusan species Clytia
hemisphaerica and Podocoryne,
expressed-sequence tagged (EST)
databases are publicly available
through NCBI dbEST, and genome
sequences are forthcoming.
Genome projects for Aurelia sp.1,
and Cladonema pacificum are also
under way. Efforts are being made to
develop molecular tools, including
RNA interference (RNAi), morpholinoantisense oligonucleotides, and
transgenesis. Arrival of such resources
should establish the jellyfish as a
valuable model to study function,
development, and the evolutionary
origins of nervous systems.
Where can I find out more?
Arai, M.N.A. (1996). Functional Biology of
Scyphozoa. (Springer).
Satterlie, R.A. (2011). Do jellyfish have central
nervous systems? J. Exp. Biol. 214, 1215–1223.
Costello, J.H., Colin, S.P., and Dabiri, J.O. (2008).
Medusan morphospace: phylogenetic
constraints, biomechanical solutions, and
ecological consequences. Invertebrate Biol.
127, 265–290.
Garm, A., Oskarsson, M., and Nilsson, D.-E. (2011).
Box jellyfish use terrestrial visual cues for
navigation. Curr. Biol. 21, 798–803.
Houliston, E., Momose, T., and Manuel, M. (2010).
Clytia hemisphaerica: a jellyfish cousin joins the
laboratory. Trends Genet. 26, 159–167.
Mackie, G.O. (2004). Central neural circuitry in the
jellyfish Aglantha: a model ‘simple nervous
system’. Neurosignals 13, 5–19.
Nakanishi, N., Yuan, D., Hartenstein, V., and Jacobs,
D.K. (2012). Evolutionary origin of rhopalia:
insights from cellular-level analyses of Otx and
POU expression patterns in the developing
rhopalial nervous system. Evol. Dev. 12,
404–415.
Nilsson, D.-E., Gislén, L., Coates, M.M., Skogh,
C., and Garm, A. (2005). Advanced optics in a
jellyfish eye. Nature 435, 201–205.
Skogh, C., Garm, A., Nilsson, D.-E., and Ekström,
P. (2006). Bilaterally symmetrical rhopalial
nervous system of the box jellyfish Tripedalia
cystophora. J. Morphol. 267, 1391–1405.
Kavli Institute for Brain and Mind, UCSD,
La Jolla, CA 92093-0126, USA.
E-mail: rgreenspan@ucsd.edu
Primer
C4 photosynthesis
Elizabeth A. Kellogg
The number of humans on earth is
increasing, generating concerns
about food security and spurring
efforts throughout the world to
increase the productivity of crops. If
a way could be found to increase the
yield of crops by, say, 20%, it would
have immense impact on global food
supplies. Fortunately, evolution has
already crafted such a mechanism,
known as C4 photosynthesis. The C4
pathway is in effect a turbocharger
for the more conventional C3 pathway.
Just as a turbocharger improves
performance of an engine by forcing
more air into the manifold, C4
improves photosynthetic performance
by forcing CO2 into the standard
C3 photosynthetic apparatus. The
added efficiency of this mechanism is
obvious at a global level. Only about
3% of flowering plant species use the
C4 pathway, but this relative handful
of species account for 23% of the
carbon fixed (primary productivity)
in the world. The pathway occurs in
several of the world’s major crops,
notably maize (corn) and sorghum,
and in many of the species in use
as biofuels, most importantly sugar
cane; all of these are grasses in the
family Poaceae. If a major C3 crop
such as rice could be bred to use the
C4 pathway, the economic impact
would be immense.
This Primer will summarize the
current state of knowledge about
C4 photosynthesis and highlight
one of its enduring mysteries —
despite years of study and deep
understanding of its physiology,
biochemistry and ecology, the trigger
for development of C4 remains
unknown. As noted in the next
section, the pathway has arisen many
times in recent evolutionary history.
The physiological, biochemical,
anatomical, and genetic data
described in the subsequent
sections all point to a process
whose complexity appears at odds
with the apparent ease with which
C4 originates. Some hints about
the controls come from the study
of photorespiration, so-called C2
photosynthesis, but, as outlined